title: Cord blood proteins and multichannel-electroencephalography in hypoxic-ischemic encephalopathy.
abstract: OBJECTIVE
  To explore the association between multiple umbilical cord blood proteins and severity of hypoxic-ischemic encephalopathy as defined by continuous multichannel electroencephalography.
  
  
  METHODS
  A prospective case-control cohort study, which was divided into separate exploratory and validation cohorts.
  
  
  METHODS
  A single tertiary neonatal intensive care facility.
  
  
  METHODS
  The study recruited full-term infants with perinatal asphyxia and controls. Identical procedures were used to recruit a representative exploratory sample (n = 30) and a subsequent validation cohort (n = 100).
  
  
  METHODS
  All had umbilical cord blood drawn and biobanked at delivery, continuous multichannel electroencephalography commenced in the first 24 hours, and a modified Sarnat score assigned. Analysis of 37 potential cord blood protein markers of hypoxic-ischemic encephalopathy was performed using Luminex multiplex assays.
  
  
  RESULTS
  Cord blood from 130 infants was analyzed. Interleukin-16 and interleukin-6 significantly differentiated between a moderate-severely abnormal and normal-mildly abnormal electroencephalography background in both exploratory (p = 0.005 and p = 0.016, respectively) and validation cohorts (p = 0.039 and p = 0.024, respectively). To develop a predictive model for a moderate-severely abnormal electroencephalography, stepwise regression analysis was used to combine these analytes with current standard clinical markers of asphyxia (pH, base deficit, and 10-min Apgar). Only Apgar score and interleukin-16 remained in the model, which was highly predictive of an abnormal electroencephalography (area under the curve [AUC] = 0.956, p < 0.001, positive predictive value = 89%, and negative predictive value = 94%).
  
  
  CONCLUSIONS
  Cord blood interleukin-6 and interleukin-16 were associated with electrographic grade of hypoxic-ischemic encephalopathy. To predict an abnormal electroencephalography, interleukin-16 and 10-minute Apgar used in combination performed better than current markers.
authors.affiliation: Neonatal Brain Research Group, Department of Paediatrics and Child Health, Cork University Maternity Hospital, Wilton, Cork, Ireland. Bh.walsh@ucc.ie
authors.forename: Brian H
authors.initials: BH
authors.lastname: Walsh
authors.forename: Geraldine B
authors.initials: GB
authors.lastname: Boylan
authors.forename: Vicki
authors.initials: V
authors.lastname: Livingstone
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Dempsey
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: Murray
mesh_terms: D001034:Apgar Score; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003661:Decision Support Techniques; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000175:diagnosis* / Q000628:therapy; D007231:Infant, Newborn; D019410:Interleukin-16 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D019410:Interleukin-16; D015850:Interleukin-6